Osimertinib improves symptoms in advanced lung cancer patients
Osimertinib improves cancer-related symptoms in patients with advanced lung cancer, according to an analysis of patient-reported outcomes from the AURA3 phase III clinical trial presented at the European Lung Cancer Conference (ELCC).1
"With my past experience conducting clinical trials, I often see new treatments that might be more effective, but are also usually more toxic," said lead author Dr Chee Lee, Medical Oncologist, St George Hospital Cancer Care Centre, New South Wales, Australia. "Osimertinib not only increases progression-free survival but it is well-tolerated, which makes a big difference for our patients."
AURA3 included 419 patients with advanced epidermal growth factor receptor (EGFR) mutation non-small-cell lung cancer (NSCLC) who had progressed after first-line EGFR-tyrosine kinase inhibitor (TKI) therapy. They were randomised to receive the oral TKI osimertinib or chemotherapy. Patients taking osimertinib had significantly longer progression-free survival of 10.1 months versus those on chemotherapy with 4.4 months (hazard ratio 0.30; 95% confidence interval 0.23, 0.41; p<0.001).2
Today researchers presented the findings on patient-reported outcomes from the AURA3 trial. Information was collected using two standardised European Organisation for Research and Treatment of Cancer (EORTC) questionnaires, the QLQ-LC13 that assessed lung cancer specific symptoms and the QLQ-C30 that assessed general cancer symptoms. Patients completed both questionnaires at baseline and then at regular intervals until disease progression and beyond. The researchers then analysed the findings to see if control of symptoms was better with osimertinib or chemotherapy.
The researchers found that osimertinib significantly reduced many lung cancer symptoms, primarily appetite loss, fatigue, breathlessness and chest pain. There was a trend for osimertinib to reduce cough but it was not statistically significant. Dr Lee said: "It generally took longer for these symptoms to get worse in patients taking the osimertinib tablet compared to chemotherapy."
In patients who had symptoms at the start of the study, appetite loss improved significantly faster on osimertinib compared to chemotherapy, and patients became less fatigued and less breathless.
Compared to chemotherapy, osimertinib significantly improved global health status, physical functioning, role functioning and social functioning scores. There was a trend towards improved emotional and cognitive function with osimertinib but it was not statistically significant. "Patients taking osimertinib were more able to do normal daily activities and socialise than those on chemotherapy," said Dr Lee.
He continued: "Patients with metastatic lung cancer receiving first-line treatment are really quite sick. Patients in the AURA3 trial had progressed on first-line treatment and were receiving second-line therapy, so they were even sicker. To be able to reduce cancer symptoms and improve quality of life in addition to progression-free survival for these patients is a major leap."
Dr Lee concluded: "For patients with incurable cancer, prolonging only progression-free survival probably has very little meaning for them. However, treatment that can additionally improve symptoms and maintain quality of life probably means a lot for these patients."
Commenting on the importance of the trial, Prof Solange Peters, Head of Medical Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, said: "The AURA3 trial has made it clear that when patients progress on first-line targeted therapy for EGFR mutation NSCLC with a T790M resistance mutation, they should stay on targeted therapy using a new generation inhibitor rather than switching to traditional chemotherapy for the second line of therapy. Patients taking second-line osimertinib had longer progression-free survival and less toxicity than those on chemotherapy."
"The data presented today shows that second-line osimertinib also significantly improved time to deterioration of important lung cancer symptoms like cough, chest pain and dyspnoea, and improved general health status," continued Peters. "Before these results clinicians had the feeling that second-line osimertinib would be efficient and better tolerated than chemotherapy but it was a subjective assumption. We now have proof that the drug has better activity, less toxicity, and improves quality of life."
Regarding the need for future studies, Peters said: "Patients with EGFR mutation NSCLC should now receive frontline TKI (first or second generation) and second-line osimertinib when they have a T790M resistance mutation. We need to know if there are options other than chemotherapy for the subsequent third line of therapy."
"We also have to keep in mind that osimertinib is only effective in the 55% of EGFR mutation NSCLC patients whose resistance to frontline TKI is caused by this T790M gatekeeper mutation," she continued. "More research is needed to find better second-line treatments for patients with a different mechanism of resistance, for whom chemotherapy is currently the only option. Finally, the opportunity for frontline prescription of osimertinib in all EGFR mutated NSCLC will be described by the FLAURA trial which is comparing first generation TKI to osimertinib as the very initial treatment and should report later this year."
2. Mok TS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629–640. DOI: 10.1056/NEJMoa1612674.